High Dose Intravenous Ascorbic Acid in Severe Sepsis

• ClinicalTrials.gov Identifier: NCT02734147
• Recruitment Status: Terminated
• First Posted: April 12, 2016
• Results First Posted: February 16, 2021
• Last Update Posted: February 16, 2021
• Sponsor: Christiana Care Health Services
• Information provided by (Responsible Party): Christiana Care Health Services

Study Description

Brief Summary:

Despite an organized treatment approach outlined in expert-consensus guidelines for sepsis with fluid resuscitation to treat hypovolemia, antibiotics to target the infectious insult, and vasopressors for hypotension, mortality rates for sepsis remain high and the incidence continues to rise, making sepsis the most expensive inpatient disease.

1. Recent research has described the therapeutic benefits associated with ascorbic acid treatment for sepsis.
2. Researchers objectives are to perform a randomized-controlled clinical trial investigating the ability of ascorbic acid(vitamin C) administration to decrease organ dysfunction in severe sepsis. The widespread occurrence of microvascular dysfunction in sepsis leading to tissue hypoxia, mitochondrial dysfunction, and adenosine triphosphate (ATP) depletion, gives rise to organ failure.
3. Patients with organ failure and sepsis (severe sepsis) are at a higher risk of death than patients with organ failure alone. Critically ill patients may have an increased requirement for ascorbic acid in sepsis and these patients frequently have levels below normal. Ascorbic acid administration, has been shown to correlate inversely with organ failure (human literature) and directly with survival (animal studies).

4,5 Intravenous ascorbic acid therapy decreases organ failure by providing a protective effect on several microvascular functions including improving capillary blood flow, decreasing microvascular permeability, and improving arteriolar responsiveness to vasoconstrictors. Defining the utility of novel agents to augment researchers care for severe sepsis is an important task as investigators continue the institutional focus on sepsis care.

Condition or disease	Intervention/treatment	Phase
Sepsis	Drug: Ascorbic Acid; Other: Normal Saline	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Efficacy of Intravenous Ascorbic Acid in Patients With Severe Sepsis
• Study Start Date: April 1, 2016
• Actual Primary Completion Date: October 8, 2017
• Actual Study Completion Date: November 23, 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: High dose IV ascorbic acid; Patients will receive 67 mg/kg IV ascorbic acid in 100 ml normal saline over 30 minutes every 8 hours (200 mg/kg/day) for 72 hours.	Drug: Ascorbic Acid
Placebo Comparator: Placebo; The placebo group will receive 100 ml 0.9% NaCl over 30 minutes every 8 hours for 72 hours.	Other: Normal Saline

Outcome Measures

Primary Outcome Measures :

1. Change in Modified SOFA Score [ Time Frame: Baseline and 72 hours ]
   Sequential Organ Failure Assessment (SOFA) Score included the degree of dysfunction of six organ systems (Respiratory, Cardiovascular, Liver, Renal, Coagulation, Neurologic. A modification of the SOFA includes the exclusion of the Liver function. Total score is reported, minimum score = 0 maximum score = 20. Higher scores indicate greater degree of dysfunction.

Secondary Outcome Measures :

1. Modified SOFA Score [ Time Frame: at 72 Hours ]
   Sequential Organ Failure Assessment (SOFA) Score included the degree of dysfunction of six organ systems (Respiratory, Cardiovascular, Liver, Renal, Coagulation, Neurologic. A modification of the SOFA includes the exclusion of the Liver function. Total score is reported, minimum score = 0 maximum score = 20. Higher scores indicate greater dysfunction.
2. Ascorbic Acid Concentration at 32 Hours [ Time Frame: 32 Hours ]
   Ascorbic Acid Concentration Normal Ascorbic Acid Range 0.4-2.0 mg/dL
3. ICU Length of Stay [ Time Frame: Length of ICU stay up to 200 hours ]
   ICU Length of Stay in Hours
4. Hospital Length of Stay [ Time Frame: From ICU admission through ICU discharge, up to 2 weeks ]
   From admission until discharge from ICU in days
5. Change in PIRO Score [ Time Frame: Baseline and 72 hours ]
   PIRO consists of 4 assessments, Predisposition (scored 0-9), Infection (scored 0-4), Response (scored 0-6), and Organ Failure (scored 0-14) (PIRO). The total PIRO score is the sum of all subscores and ranges from 0-33 with higher scores indicating worse health.
6. Percentage of Participants Who Died [ Time Frame: From initial hospital admission through discharge, up to 2 weeks. ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Patients with:

1. A suspected or confirmed infection with an order for intravenous antibiotics or antivirals
2. The presence of acute sepsis-induced organ dysfunction

Definition of organ dysfunction:

1. Arterial hypoxemia [PaO2 /FiO2 < 300]
2. Hypotension [systolic blood pressure (SBP) < 90 mmHg or SBP decrease > 40 mmHg]
3. Lactic acidosis [lactate > 2.5 mmol/L]
4. Acute kidney injury [creatinine >2.0 or urine output < 0.5 ml/kg/hr for >2 hours despite fluid resuscitation]
5. Thrombocytopenia [platelet count < 100,000]
6. Acute coagulopathy [international normalized ratio (INR) > 1.5]
7. Hepatic failure [bilirubin > 2 mg/dL].
8. Predisposition, Infection, Response, and Organ Failure (PIRO) score ≥ 10

Exclusion Criteria:

1. Age < 18 years
2. Pregnancy or breastfeeding
3. Requirement for immediate surgery within the treatment protocol timeframe
4. Inability to obtain written informed consent from subject or surrogate
5. Patient to receive comfort measures only

Contacts and Locations

Locations

United States, Delaware

Chrisitana Care Health System-Christiana Hospital

Newark, Delaware, United States, 19718

Sponsors and Collaborators

Christiana Care Health Services

Investigators

• Principal Investigator: Ryan Arnold, MD; Christiana Care Health Services
• Principal Investigator: Jamie Rosini, PharmD; Christiana Care Health Services

  Study Documents (Full-Text)

Documents provided by Christiana Care Health Services:

Study Protocol and Statistical Analysis Plan  [PDF] January 11, 2017

More Information

• Responsible Party: Christiana Care Health Services
• ClinicalTrials.gov Identifier: NCT02734147
• Other Study ID Numbers: 603204
• First Posted: April 12, 2016
• Results First Posted: February 16, 2021
• Last Update Posted: February 16, 2021
• Last Verified: January 2021

Additional relevant MeSH terms:

Sepsis; Toxemia; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Ascorbic Acid; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Vitamins; Micronutrients